There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow-up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last followup. The HPV-positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV-positive group, after adjusting for clinicopathological factors, patients with cyclin D1-positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1-negative tumors. However, within the HPV-negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes.Insight into molecular pathways underpinning carcinogenesis has opened the way for a new generation of molecular markers to predict cancer outcome. There is increasing use of combinations of molecular prognostic markers in human cancer.1,2 Many squamous cell carcinomas of the oropharynx arise following disruption of the p53 and/or the retinoblastoma (pRb) pathways by mutagens present in tobacco or alcohol. However, it is now accepted that up to 60% of oropharyngeal cancers are induced by human papillomavirus (HPV). [3][4][5][6][7] In the HPV-induced subset, the p53 and pRb pathways are inactivated by the HPV E6 and E7 oncoproteins, respectively. HPV-induced cancers appear biologically distinct; most notable is their more favorable prognosis. 8,9 Retinoblastoma (pRb) pathway proteins (p16 ink4 , cyclin D1

Background: Therapeutic and elective dissection of the neck is accepted management in the treatment of squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT). Accurate histological assessment of the levels of involvement of cervical metastatic spread from different sites within the UADT has allowed the increasing use of less than radical procedures, with associated reduced morbidity. Methods: A total of 168 necks in 126 patients were examined pathologically. All levels were identified at surgery, marked and orientated by pinning the specimen to a cork board, and examined histologically. A total of 114 necks had a comprehensive neck dissection (CND) in which all levels were dissected. The number and level of involvement and the occult rate (1 14 necks) for each primary site was assessed. Of the total of 168 necks, 80 had pathologically involved nodes, and the number with greater than one node involved (NJ was compared for each primary site. The number with extracapsular spread for each nodal staging was also examined. Results: The sites of primary SCC were the oral cavity, oropharynx, hypopharynx, supraglottic and glottic larynx. In those patients with a primary in the oral cavity, no patient had level 5 involvement, but in two patients (7%) level 4 was involved. In the oropharynx, level 1 and 5 were involved in two patients (11%) each. In the hypopharynx, level 1 was not involved in any patient, however, level 5 contained metastasis in 7 (23%). In the supraglottic larynx, level 1 was involved in one (4%) patient and level 5 was involved in three (1 1%). In the glottis only one patient had bilateral multiple nodes which included level 5. In no case was level 5 involved without positive nodes in other levels. The occult rate for each primary site was 45%, 22%, 77%, 54% and 29%, respectively. The multiple node rate in the 80 necks with positive nodes was, respectively, 31%, 54%, 66%, 45% and 40%. All patients with a node larger than 3 cm had extracapsular spread of tumour. Conclusions: The level of nodal involvement and therefore the type of neck dissection should be determined by the site of the primary within the UADT and the presence or absence of nodes at surgery. There is a high number (39-66%) of pathologically involved necks which have multiple nodes and also nodes with extracapsular spread of tumour, which may influence the decision for postoperative radiotherapy.

A 41-year-old Caucasian woman presented with a painful, red right eye with minimal systemic symptomatology, and was initially diagnosed with right idiopathic orbital inflammation. Ten days later, she developed abdominal and respiratory symptoms; this led to her demise within a further week. Post-mortem examination demonstrated widespread extranodal NK/T- cell lymphoma (nasal type), involving the right posterior orbit, lungs, uterus, left adrenal gland, pericardium and meninges. Thorough physical examination with early orbital biopsy should be considered to exclude underlying treatable pathology in managing patients with presumed idiopathic orbital inflammation.

We describe two women with a misdiagnosed fracturing bone disease who were treated erroneously with i.v. zoledronate. Over the next year, they suffered marked clinical and radiographic deterioration in skeletal disease. Both were eventually diagnosed with hypophosphatemic osteomalacia secondary to acquired Fanconi syndrome (caused by light‐chain myeloma in one case and tenofovir treatment in the other). Appropriate treatment with phosphate supplementation was instituted with clinical improvement. These cases illustrate the importance of not missing osteomalacia in adults presenting with fractures, and the potentially damaging effects of treatment with long‐acting inhibitors of bone resorption in these circumstances. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Despite being a tropical country, vitamin D deficiency is common in Singapore. All young Singaporean males between the age of 18 and 21 years have to undergo mandatory military service. Stress fractures occur in military recruits, and risk factors include a sudden increase in physical activity and vitamin D deficiency. We report the bone histomorphometry findings from a case of bilateral tibial stress fractures in an 18-year-old military recruit who had vitamin D deficiency. The histomorphometry showed a mixed osteomalacia and osteoporosis pattern. This case is unique as it shows that stress fractures from a marching exercise can occur in apparently healthy well young man with vitamin D deficiency despite living in a tropical country.